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| Status |
Public on Dec 24, 2009 |
| Title |
Prkar1a haploinsufficiency leads to an overall increase in tumors caused by other genetic defects or chemical induction |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
[original title] Prkar1a haploinsufficiency in mice leads to an overall increase in tumors caused by other genetic defects or chemical induction
We investigated the Prkar1a+/- mice when bred within the Rb1+/- or Trp53+/- genetic backgrounds, or treated with a 2-step skin carcinogenesis protocol. Prkar1a+/-Trp53+/- mice developed more bone sarcomas than Trp53+/- mice (p<0.05) and Prkar1a+/-Rb1+/- mice grew more and larger pituitary and thyroid tumors than Rb1+/- mice. All mice with double heterozygosity had significantly reduced life-spans compared with their single-heterozygous counterparts. Finally, Prkar1a+/- mice developed more papillomas than wild-type animals when treated with a 2-step skin carcinogenesis protocol. A whole-genome transcriptome profiling of tumors produced by all three models identified Wnt signaling as the main pathway activated by abnormal cAMP signaling in these tissues, along with (expected) cell cycle gene abnormalities, all confirmed by qRT-PCR array and immunohistochemical analyses.
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| Overall design |
Total RNA obtained from skin papillomas from Prkar1a+/- mice were compared to those obtained from WT mice.
Total RNA obtained from pituitary and thyroid tumors from Rb1+/- mice were compared to those samples obtained from Prkar1a+/- Rb1+/- mice. Total RNA obtained from sarcomas from Tp53+/- mice were compared to those samples obtained from Prkar1a+/- Tp53+/- mice.
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| Contributor(s) |
Almeida MQ, Nesterova M, Stratakis CA, Cheadle C, Watkins T |
| Citation(s) |
20080939 |
| Submission date |
Dec 18, 2009 |
| Last update date |
Jun 14, 2018 |
| Contact name |
Madson Q Almeida |
| E-mail(s) |
madsonalmeida@usp.br
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| Phone |
301 451 3768
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| Fax |
301 402 0574
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| Organization name |
NIH
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| Department |
Section on Genetics and Endocrinology / NICHD
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| Lab |
Dr. Stratakis Lab
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| Street address |
10 Center Drive, MSC 1103
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892-1103 |
| Country |
USA |
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| Platforms (1) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
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| Samples (23)
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| Relations |
| BioProject |
PRJNA122465 |
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